Native low density lipoprotein-induced calcium transients trigger VCAM-1 and E-selectin expression in cultured human vascular endothelial cells.

Allen, Stuart; Khan, Shabeena; Al‐Mohanna, Futwan; Batten, Puspa; Yacoub, Magdi

doi:10.1172/jci445

Cited by 107 publications

(66 citation statements)

References 57 publications

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“…In smooth muscle cells and endothelial cells, LDL induced the phosphoinositidedependent signaling pathway leading to an increase in cytosolic-free calcium through pertussis toxin-sensitive GTP-binding protein (47)(48)(49). In our study, monocytes responded similarly, and LDL induced a rapid and transient increase of the [Ca 2ϩ ] i .…”

Section: Discussionmentioning

confidence: 99%

LDL activates signaling pathways leading to an increase in cytosolic free calcium and stimulation of CD11b expression in monocytes

Han

Chen

Chang

et al. 2003

Journal of Lipid Research

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In the present study, we investigated the mechanisms by which plasma lipoproteins modulate the integrindependent adhesion properties of monocytes. LDL induced the expression of the monocyte CD11b in vitro as well as in vivo via intracellular signaling mechanisms involving calcium transients. The effect on CD11b transcription was specific for native LDL and was blocked by a neutralizing anti-LDL receptor antibody. Neither oxidized LDL nor HDL had any effect on CD11b expression. Although LDL stimulated CD11b surface expression, the integrins were not activated. To initiate the CD11b-specific adhesion to the endothelium, the engagement of chemokine receptor CCR2 and intact chemokine-to-integrin signaling was necessary. However, the activation of CCR2 with monocyte chemoattractant protein-1 not only stimulated the integrins preexisting on the cell surface, but also increased the number of CD11b molecules on the cell surface. This was particularly pronounced in THP-1 cells after treatment with LDL. In a previous study, we showed that LDL induces the expression of CCR2 in monocytes. We conclude that this may be the underlying cause of the enhanced chemokine effect on CD11b expression and activation observed with these

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Section: Discussionmentioning

confidence: 99%

LDL activates signaling pathways leading to an increase in cytosolic free calcium and stimulation of CD11b expression in monocytes

Han

Chen

Chang

et al. 2003

Journal of Lipid Research

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“…In some experiments, HCAEC were preincubated with BAPTA/AM (10 M) for 30 min before the addition of nucleotides. U937 cells were labeled with the green fluorescent dye PKH2, as described previously (20). Labeled U937 cells (10 6 cells/well) were added to confluent cultures of HCAEC for 1 h at 37°C.…”

Section: Methodsmentioning

confidence: 99%

The P2Y2 Nucleotide Receptor Mediates UTP-induced Vascular Cell Adhesion Molecule-1 Expression in Coronary Artery Endothelial Cells

Seye

Jain

et al. 2003

Journal of Biological Chemistry

108

114

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Extracellular nucleotides cause a wide range of cellular responses and appear to play a role in the regulation of many vascular functions (1, 2). Vascular cells release nucleotides when exposed to stimuli such as ischemia, hypoxia, and chemical or mechanical stress (3, 4). It also is becoming apparent that extracellular nucleotides can promote the development of a variety of pathologies including disorders of the immune system, and neurodegenerative and vascular diseases (1). Indeed, ATP or UTP induces proliferation and migration of vascular smooth muscle cells, two processes involved in the development of intimal lesions found in atherosclerosis and post-angioplasty restenosis. The biological effects of extracellular nucleotides are mediated through activation of P1 and P2 purinergic receptors. P1 receptors are responsive to adenosine, whereas P2 receptors are activated by a variety of nucleotides including ATP and UTP (5, 6). The P2 receptors are subdivided into two distinct categories, the metabotropic Gprotein-coupled (P2Y) receptors and the ionotropic ligandgated channel (P2X) receptors (6, 7). Vascular cells have been shown to express metabotropic P2Y and ionotropic P2X receptors (5, 8). It has been reported that P2Y 2 receptors are upregulated in cells of rat intimal lesions following balloon angioplasty (9). Our recent studies showed that placement of a silicone collar around the rabbit carotid artery promoted upregulation of P2Y 2 receptors in vascular smooth muscle cells and endothelium (10). Subsequently, local infusion of UTP was shown to stimulate intimal hyperplasia and increase intimal monocyte infiltration (10), suggesting a role for P2Y 2 receptors in the recruitment of blood monocytes leading to inflammation in atherosclerosis.Monocyte recruitment into the vessel wall is a complex process that includes cell rolling, firm attachment, and directed migration. It is now becoming evident that adhesion molecules such as VCAM-1 play an important role in leukocyte adherence to vascular endothelial cells (11,12). VCAM-1 expression is induced or up-regulated by proinflammatory cytokines such as TNF-␣ 1 and interleukin 1-␤ on cellular components of the arterial wall including endothelial cells, smooth muscle cells, and fibroblasts (13-15). ATP and UTP have been shown to induce cell-cell adhesion in a monocyte/macrophage lineage and neutrophil adherence to an endothelial cell monolayer (16,17), raising the possibility that released ATP and UTP could induce endothelial cell activation by an autocrine/paracrine mechanism to regulate leukocyte adherence.

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“…Previous studies have shown that native LDL induces vasoconstriction, 10 impairment of endothelium-dependent relaxation, 11,12 changes in intracellular calcium flux, 13 and VSMC proliferation. 14,15 Since the effects evoked by native LDL can be blocked by compounds inhibiting different intracellular pathways, even in the absence of the classical LDL receptor, 16 it is possible that LDL signals via a rather nonspecific second messenger, such as modulation of the cellular redox balance.…”

mentioning

confidence: 97%

Native LDL Induces Proliferation of Human Vascular Smooth Muscle Cells via Redox-Mediated Activation of ERK 1/2 Mitogen-Activated Protein Kinases

et al. 2002

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Abstract-This study investigated mechanisms underlying native low-density lipoprotein (LDL)-stimulated proliferation of human vascular smooth muscle cells (VSMC). Experiments were performed to determine whether native LDL affects reactive oxygen species (ROS) formation and activity of extracellular signal-regulated kinase 1/2 (ERK1/2), and whether redox-sensitive pathways contribute to LDL-induced cell proliferation. Native LDL (100 g/mL, 24 hours) increased cell proliferation (to 303 to 388% of control, PϽ0.

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Native low density lipoprotein-induced calcium transients trigger VCAM-1 and E-selectin expression in cultured human vascular endothelial cells.

Cited by 107 publications

References 57 publications

LDL activates signaling pathways leading to an increase in cytosolic free calcium and stimulation of CD11b expression in monocytes

LDL activates signaling pathways leading to an increase in cytosolic free calcium and stimulation of CD11b expression in monocytes

The P2Y2 Nucleotide Receptor Mediates UTP-induced Vascular Cell Adhesion Molecule-1 Expression in Coronary Artery Endothelial Cells

Native LDL Induces Proliferation of Human Vascular Smooth Muscle Cells via Redox-Mediated Activation of ERK 1/2 Mitogen-Activated Protein Kinases

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